DIFFERENTIAL PATTERNS OF T-CELL RECEPTOR BV-SPECIFIC ACTIVATION OF T-CELLS BY GP 120 FROM DIFFERENT HIV STRAINS

Studies by several groups have suggested that HIV infection in vivo re sults in a BV-specific alteration of the TCR repertoire and that this might play a role in the pathogenesis of AIDS. Our earlier studies dem onstrated that both a crude extract of HIV451 as well as purified gp16 0 from HIV451 could specifically activate, in vitro, T cells expressin g a common set of TCRBV segments (TCRBV3, 12, 14, 15, and sometimes BV 17 and 20) in individuals of disparate HLA type. Furthermore, purified gp120 from HIV451 was shown to have a similar ability to activate T c ells, although with a slightly different TCRBV-specific pattern. In or der to determine whether gp120 from other HIV strains could similarly activate T cells in a TCRBV-specific pattern, PBMC from HIV seronegati ve individuals of disparate HLA type were stimulated with gp120 from t hree strains of HIV (451, IIIB, and MN). The authors found that gp120 from all three strains activate T cells bearing TCRBV2 and BV3 in near ly every individual. T cells expressing other BV segments are also act ivated, but this is more variable and appears to be unique to each ind ividual. Furthermore, gp120(451) and gp120 from HIVIIIB and HIVMN diff er in their ability to activate T cells expressing these other TCRBV s egments. These observations suggest that variation in the structure of gp120 and in the genetic and/or environmental background of the indiv idual play an important role in determining which TCRBV segments are ' triggered' by gp120. Furthermore, these observations may have importan t implications for the rate of disease progression in HIV-infected ind ividuals.